Upregulation of IFN-gamma and MHC class II expression has been studied in tumor models and is found to be effective for the control of a number of types of cancer. Treatment with IFN-gamma, the main inducer of MHC class II,can promote tumor rejection by activating immune responses. The purpose of this proposal is to identify genes which are essential for the induction of MHC class II gene expression by IFN-gamma. This will be accomplished by using gene complementation to determine the defect in G2A and G3A mutant cell lines, both of which are - selectively defective in IFN- gamma induction of class II-associated genes, but not in the IFN- gamma induction of the classical pathway. As a complementary approach, an antisense library will be used to identify additional genes selectively required for MHC class II induction by IFN- gamma. This work should promote the treatment of cancer through the identification of potential targets for the enhancement of tumor rejection by immunotherapy.